The use of light in the treatment of various skin diseases has been around for centuries. This field termed phototherapy uses a combination of small molecules that can absorb light in the visible, UV-A, and near-infrared range. Phototherapy is comparable to radiotherapy in its efficacy. However unlike radiotherapy and chemotherapy, phototherapy lacks the nonspecific toxicity seen in radiotherapy and chemotherapy and because of this, phototherapy can be given on more regular intervals.
Photodiagnostic therapy (PDT) is an experimental technology that relies on the ability of fluorescent small molecules to preferentially accumulate in diseased tissues. Due to this preferential retention, it is possible to distinguish between normal and diseased tissue. It is thought that these small molecules in tumorgenic tissues may accumulate due to a decrease in intracellular pH, an increase in low density lipoproteins, and abnormal membrane composition1.
It is generally accepted that small nonpolar molecules can pass through the plasma membrane of a cell by simple diffusion3. Evidence for this has been described in the uptake of adriamycin, quinone, and rhodamine 123 in unilamellar and transbilayer vesicles4,5. Simple diffusion has also been used to describe the uptake of doxorubicin, daunorubicin, and rhodamine 123 in cultured transformed and normal cells1,6,7.
Photodynamic therapy (PDT) is an emerging minimally invasive therapy for the treatment of cancer, age-related macular degeneration, psoriasis and a host of other chronic diseases. PDT employs the use of photosensitizing agents in combination with light to disrupt cellular functions, which ultimately leads to cell death. The intracellular location of photosensitizing agents also plays critical role in the mode of action in cellular toxicity. Most photosensitizers used in clinical, and experimental treatment of cancer are localize in cytoplasmic organelles of a cell.8 Photosensitizing agents are compounds that absorb a specific wavelength of light which then reacts with molecular oxygen to generate a reactive oxygen species. These reactive oxygen species such as H2O2, NO, and −OH are the true perpetrators of the cellular toxicity seen in PDT.
Psoralen is commonly used in PDT to treat skin diseases (e.g., Eczema, Psoriasis and Vitiligo, and mycosis fungoides). However, psoralen is not a chemotherapeutic agent by itself, and therefore is not effective without the application of energy in the form of light.
Although great strides have been made in photodynamic therapy, a need exists for a photosensitizing agent that will selectively accumulate in diseased cells and act as a chemotherapeutic agent (even without the application of light).